Ghrelin is a gut hormone with potent orexigenic and growth hormone release stimulatory effects, and is the first known endogenous ligand of the growth hormone secretagogue receptor. A notable feature of ghrelin is that it carries an acyl group, in most cases an octanoyl group, in the third serine. While it has been shown that the acylation is critical for the majority of ghrelin functions, the mechanisms of acylation of ghrelin remained poorly understood. In 2008, it was discovered that ghrelin O-acyltransferase (GOAT) is the enzyme responsible for acylating ghrelin. GOAT is highly conserved from zebrafish to humans. It is most abundant in the stomach and pancreas. GOAT mRNA expression is regulated by energy balance, being upregulated by energy restriction and downregulated by energy abundance. GOAT attenuation using synthetic inhibitors enhances insulin secretion and reduces body weight. GOAT inhibitors are currently being developed for the treatment of metabolic disorders. In addition to its ghrelin mediated effects, GOAT is also known to directly regulate bile acid secretion. The discovery of GOAT helped to redefine the ghrelin research field and enabled the development of another target molecule for potential therapies aimed to prevent/treat diabetes and obesity.